Efficacy Study Comparing Velcade Dexamethasone Thalidomide Versus Velcade Cyclophosphamide Dexamethasone as Induction Treatment in the Initial Management of Multiple Myeloma (IFM2013-04)

Inclusion Criteria: Patients newly diagnosed with symptomatic Multiple Myeloma (MM) patient

1. • 18 ≤ age < 66 years
2. • Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2
3. • Patients must be eligible for Autologous Stem Cell Transplantation
4. • Patients must have measurable disease by serum M-protein ≥ 10 g/L and/or urineM-protein ≥200mg/day
5. • Female patients of child-bearing potential (FCBP):

• Must agree to have medically supervised pregnancy tests prior to starting studyand every 21 days, including 4 weeks after the end of study treatment. Thisapplies even if the patient practices complete and continued sexual abstinence.

• Must agree to use and be able to comply with effective contraception withoutinterruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days afterdiscontinuation of study therapy.

6. • Male Patients:

• Must agree to use a condom during sexual contact with a FCBP, throughout studydrug therapy, during any dose interruption and for one week after discontinuationof study therapy

• Must agree to not donate semen during study drug therapy and for one week afterdiscontinuation of study therapy

7. • All patients must:

• Agree to abstain from donating blood while taking study drug therapy and for oneweek after discontinuation of study drug therapy

• Agree not to share study medication with another person.

8. • Patients must be capable of giving informed consent
9. • Patients must be affiliated with French social security system

Exclusion Criteria:

1. • Asymptomatic Multiple myeloma
2. • Non-secretory Multiple myeloma
3. • Proven AL-amyloidosis
4. • Age ≥ 66 years old
5. • Prior or current systemic therapy for Multiple myeloma, including steroids (exceptfor emergency use of a 4-day block of dexamethasone before randomization, maximumtotal dose allowed 160 mg)
6. • Radiation therapy in the 2 weeks preceding randomization
7. • National Cancer Institute grade ≥ 2 peripheral neuropathy
8. • Haemoglobin < 8g/dL
9. • Absolute neutrophil count < 1,000 cells / µL, platelet count < 50,000 cells / µL
10. • Creatinine level > 170 µmol/L or requiring dialysis.
11. • Bilirubin, transaminases or GamaGT > 3 UNL (upper normal limit)
12. • Positive HIV serology, evidence of active Hepatitis B and C infection
13. • Severe active infection
14. • Inability to comply with an anti-thrombotic treatment regimen
15. • A personal medical history of severe psychiatric disease
16. • Uncontrolled diabetes contraindicating the use of high-dose dexamethasone
17. • Non-controlled or severe cardiovascular disease (including a myocardial infarctionin the 6 months prior to recruitment)
18. • A personal medical history of cancer unless the patient has been without relapseafter treatment discontinuation > or = 5 years (except for basocellular skin cancer orin situ cervical cancer)
19. • Use of any investigational drug in the 30 days preceding randomization

22 - Pregnant or lactating women. 23 - Adults under juridical protection 24 - Known orsuspected hypersensitivity to any of the study therapies or excipients 25 - Necessity ofvaccination for yellow fever or with any other live vaccines